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Nature:超高亲和力蛋白质复合物的高度失调

生物医学中文摘要 2018-11-22 10:04:38


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组蛋白H1和前胸腺素-α的高亲和力复合物揭示了意想不到的相互作用机制,其中大的相反净电荷使得两种蛋白质即使在复合物中也保持高度失调。

【题目】超高亲和力蛋白质复合物的高度失调

【摘要】生物学中的分子通讯由蛋白质相互作用介导。根据目前的范例,这些相互作用所需的特异性和亲和力被编码为结合界面的精确互补性。即使在生理条件下无序或含有大量非结构化区域的蛋白质通常与其他生物分子上结构良好的结合位点相互作用。在这里我们展示了一个意想不到的相互作用机制的存在:两个本质上无序的人类蛋白质组蛋白H1和它的核蛋白前胸腺素-α在与皮摩尔亲和力的复合物中缔合,但完全保留其结构失调、远程灵活性和高度动态特性。在紧密结合的实验和分子模拟的基础上,我们表明相互作用可以通过两种蛋白质的大的相反净电荷来解释,而不需要定义结合位点或特定个体残基之间的相互作用。蛋白质组范围的序列分析表明这种相互作用机制在真核生物中可能是丰富的。


英文原文

A high-affinity complex of histone H1 and prothymosin-α reveals an unexpected interaction mechanism, where the large opposite net charge enables the two proteins to remain highly disordered even in the complex.


【title】Extreme disorder in an ultrahigh-affinity protein complex

【authors】Alessandro Borgia, Madeleine B. Borgia, Katrine Bugge, Vera M. Kissling, Pétur O. Heidarsson, Catarina B. Fernandes, Andrea Sottini, Andrea Soranno, Karin J. Buholzer, Daniel Nettels, Birthe B. Kragelund, Robert B. Best & Benjamin Schuler

【abstract】Molecular communication in biology is mediated by protein interactions. According to the current paradigm, the specificity and affinity required for these interactions are encoded in the precise complementarity of binding interfaces. Even proteins that are disordered under physiological conditions or that contain large unstructured regions commonly interact with well-structured binding sites on other biomolecules. Here we demonstrate the existence of an unexpected interaction mechanism: the two intrinsically disordered human proteins histone H1 and its nuclear chaperone prothymosin-α associate in a complex with picomolar affinity, but fully retain their structural disorder, long-range flexibility and highly dynamic character. On the basis of closely integrated experiments and molecular simulations, we show that the interaction can be explained by the large opposite net charge of the two proteins, without requiring defined binding sites or interactions between specific individual residues. Proteome-wide sequence analysis suggests that this interaction mechanism may be abundant in eukaryotes.



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